Health and economic impact of subcutaneous allergen immunotherapy in patients with pollen-induced allergic rhinoconjunctivitis: real-word evidence from the Czech Republic.

Background: The prevalence of allergic rhinoconjunctivitis (AR) has been increasing over the years, and allergen immunotherapy (AIT) remains the only disease-modifying treatment. However, cost-effectiveness data remain scarce. Methods: In this single-arm, noninterventional, prospective, multicenter study, we describe the effectiveness, safety and costs of subcutaneous AIT for pollen-induced allergic rhinoconjunctivitis. Results: Of 471 new AIT users, 317 completed three courses of treatment, and symptoms improved in 96%; no serious adverse reactions were reported. The cost of symptomatic medication decreased by 49% and the cost of unscheduled specialist visits decreased by 73%. Except for AIT administration, total healthcare costs decreased by 54% compared with the baseline pollen season without AIT. Conclusion: In clinical practice, subcutaneous AIT is an effective treatment generating savings on symptomatic medication and unscheduled consultations.

Hay fever has become more frequent over the years, and allergen immunotherapy (AIT) remains the only treatment able to reduce both symptoms and the root cause of this condition. However, it is not clear whether the benefits outweigh the price of the therapy. In this study, we observed patients in the common practice and described the effectiveness, safety and costs of injected AIT for pollen-induced hay fever. Of 471 new AIT users, 317 completed three courses of treatment in 3 consecutive years. Symptoms improved in 96% of them; no serious adverse reactions were reported. The cost of symptom-relieving medication decreased by 49% and the cost of unscheduled physician visits decreased by 73%. Except for costs related to AIT administration, total healthcare costs decreased by 54% compared with the years before AIT. In clinical practice, injected AIT is an effective treatment which generates savings on other medication and unscheduled physician consultations.

Regulatory Requirements for the Quality of Allergen Products for Allergen Immunotherapy of Food Allergy.

PURPOSE OF REVIEW: Medicinal products for allergen immunotherapy (AIT) of food allergies have gained enormous momentum in recent years. With this new class of products entering marketing authorization procedures, compliance to regulatory requirements becomes a critical element. Here, an overview is provided on specific requirements and aspects concerning the quality control and manufacturing of these products. RECENT FINDINGS: Recent developments in the field of AIT for food allergies are divers, including products for oral, epicutaneous, and subcutaneous application, most notably targeting egg, milk, and peanut allergy. As the source materials for food AIT product are typically produced for food consumption and not for medicinal purposes, unique challenges arise in the manufacturing processes and controls of these medicinal products. Individual approaches are needed to assure acceptable quality, including control of relevant quantitative and qualitative characteristics. Major characteristics for quality verification include determination of protein content, total allergenic activity, and major allergen content. The applied manufacturing processes need to be established such that relevant process parameters are kept within justified limits and consistency of produced batches is assured. Allergen products for food AIT present specific challenges with respect to quality aspects that differentiate them from other commonly available AIT products. While established regulation is available and provides clear guidance for most aspects, other issues require consideration of new and individual settings relevant here. Consequently, as experience grows, respective amendments to currently available guidance may be needed.

Providing cost-effective care for food allergy.

OBJECTIVE: To review the cost-effectiveness of food allergy management strategies. DATA SOURCES AND STUDY SELECTIONS: A narrative review and synthesis of literature identified using a PubMed search of relevant articles describing cost-effectiveness evaluations of food allergy management. RESULTS: Screening at-risk infants for peanut allergy carries risk of overdiagnosis and is not cost-effective. Evidence suggests that cost-effective care could be better optimized by minimizing delay in oral food challenges for eligible patients, clarifying the role of precautionary allergen labeling, incorporating patient-preference sensitive care in activation of emergency medical services for resolved allergic reactions, and considering value-based pricing and school-supply models for epinephrine. Finally, the annual value-based cost (willingness to pay [WTP] $100,000/quality-adjusted life years [QALY]) of peanut immunotherapy has been estimated to be between $1568 and $6568 for epicutaneous immunotherapy (EPIT) and between $1235 and $5235 for probiotic with peanut oil immunotherapy (POIT), with each therapy showing more favorable cost-effectiveness with greater improvements in health utility, particularly if sustained unresponsiveness can be achieved. CONCLUSION: Many aspects of food allergy management are not cost-effective, and recent evaluations suggest a greater role for incorporating patient and family preferences into guideline-based and traditionally reflexive management decisions. Caregiver understanding of food allergy screening tradeoffs is critical, given that screening children before allergen exposure has significant costs and results in overdiagnosis, especially when oral food challenges are omitted from diagnostic algorithms. Cost-effectiveness analysis can help to identify important decision levers in patient management across a wide range of topics. Further research is needed to better understand health state utilities of specific patient populations.

Compliance With Subcutaneous Immunotherapy Appointments in an Urban Tertiary Care Setting.

INTRODUCTION: Subcutaneous immunotherapy (SCIT) is an effective treatment for allergic disease such as allergic rhinitis and asthma. Reported adherence rates to SCIT have been low, ranging between 50% and 89%. This study sought to evaluate compliance to SCIT in an urban "safety net," tertiary care center, and to evaluate for disparities in compliance based upon insurance and socioeconomic status. METHODS: A retrospective chart review of SCIT patients between 2003 and 2016 was performed. Demographic data, insurance carriers, and comorbidities were collected. Compliance was evaluated on treatment adherence (percentage of injections administered/scheduled appointments). Statistical analysis was performed using R statistical software. Linear regression analysis was performed to compare compliance to the variables, asthma, duration of therapy, payor, and age. Analysis of variance was used to compare mean compliance between payor groups. RESULTS: Two hundred five patients met our inclusion criteria and 28 were excluded. Insurance composition was Medicaid (67, 33%), Medicare (18, 9%), Health Safety Net (HSN) in Massachusetts (33, 16%), and commercial payors (82, 42%). Linear regression demonstrated that age, duration of therapy, and asthma status were not related to the percentage of missed doses ( P > .05). Payor status was statistically predictive of missed doses ( P = .02). When comparing average percentage of missed immunotherapy shots, Medicaid patients missed the most 34.2%, followed by Medicare 24.4%, commercial insurance 19.9%, and HSN in Massachusetts 18.5% ( P ≤ .02). CONCLUSION: In a cohort of patients at a tertiary care "safety-net" center serving a low-income population, compliance to SCIT was found to be overall high but lower in the Medicaid population.

Cost-effectiveness of grass pollen subcutaneous immunotherapy (SCIT) compared to sublingual immunotherapy (SLIT) and symptomatic treatment in Austria, Spain, and Switzerland.

BACKGROUND: While specific immunotherapy (SIT) has been proven to be cost-effective for the treatment of allergic rhinitis compared to symptomatic treatment, there is a lack of European studies in which sublingual (SLIT) and subcutaneous (SCIT) immunotherapy were compared. The present analysis is focused on the cost-effectiveness of SCIT compared to SLIT and symptomatic treatment of grass pollen allergy in Austria, Spain, and Switzerland. It will address specific properties of the underlying healthcare systems. METHODS: The investigation is based on a previously published health economic model calculation. This was designed as a Markov model with pre-defined health stages and a duration of 9 years covering specific preparations for SCIT (Allergovit) and SLIT (Oralair). The effectiveness was assessed as symptom-score based quality-adjusted life years (QALYs). Additionally, total cost has been determined as well as the cost-effectiveness of SCIT. The robustness of model results was proved in further sensitivity analyses. RESULTS: With regard to the effectiveness of both SCIT and SLIT, preparations were dominant compared to pharmacological symptomatic therapy. Both strategies were associated with additional cost, but, combined with the results on effectiveness, both have to be regarded as cost-effective. A direct comparison of the SCIT (Allergovit) and SLIT (Oralair) showed lower total costs of SCIT vs SLIT for Austria, Spain, and Switzerland (€1,368 vs €2,012, €2,229 vs €2,547, and €1,901 vs €2,220) and superior effectiveness (SCIT =8.02 QALYs; SLIT =7.98 QALYs; and symptomatic therapy =7.90 QALYs). CONCLUSION: In patients with allergic rhinitis, SIT offers cost-effective treatment options compared to symptomatic treatment. When comparing SCIT (Allergovit) and SLIT (Oralair), SCIT was dominant in terms of QALYs as well as costs, in particular due to a slightly higher patient compliance and lower drug costs.

Comparative effectiveness of allergy testing method in driving immunotherapy outcomes.

BACKGROUND: Skin-prick testing (SPT), in vitro testing (IVT), and intradermal-dilutional testing (IDT) are methods to detect patient sensitivities to specific allergens and direct immunotherapy dosing. We used objective and subjective measures of improvement to compare outcomes based on test method. METHODS: Patients underwent 1 of 3 protocols: SPT, screening SPT followed by IDT, or IVT. We used institution billing data to do a cost analysis of these tests. The time to maintenance (TTM) therapy was analyzed and patients were stratified into high and low reactors. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used to quantify symptoms pre-maintenance and post-maintenance. RESULTS: Of 177 patients (SPT, n = 40; IVT, n = 91; IDT, n = 46), 115 (SPT, n = 35; IVT, n = 39; IDT, n = 41) were high reactors. Out of 90 patients (SPT, n = 17; IVT, n = 37; IDT, n = 36) reaching maintenance, 58 were high reactors (SPT, n = 15; IVT, n = 12; IDT, n = 31). Overall, SPT, IVT, and IDT median TTM were 542, 329, and 578.5 days, respectively. IDT TTM was shorter compared to IVT overall and in high reactors (hazard ratio [HR] = 1.91, p = 0.02; HR = 2.12, p = 0.03), but was not significant compared to SPT high reactors (p = 0.33). The IDT cost was $62.66, translating to an incremental cost-effectiveness ratio of $0.23 per day of shortened TTM. Median RQLQ change for the SPT, IVT, and IDT groups was 6.5, 1, and 1.5, respectively, but was not significant (p = 0.60). CONCLUSION: IDT reached maintenance immunotherapy quicker than IVT but there was no difference compared to SPT. TTM did not correlate with improvements in patient symptoms between testing methods. This study represents a novel comparison of outcomes based on initial allergy testing method.

An Economic Analysis of a Peanut Oral Immunotherapy Study in Children.

BACKGROUND: Peanut oral immunotherapy (POIT) decreases the probability of accidental recurrent systemic reactions but reactions from the therapy itself are frequent. OBJECTIVE: The purpose of this economic analysis was to characterize the potential cost-effectiveness of POIT. METHODS: Cohort simulations were used to evaluate the effect of POIT for children with peanut allergy. A POIT with probiotic was used in the base-case simulation and long-term survival was modeled using age-adjusted mortality together with the risk of food allergy-associated mortality. RESULTS: The incremental POIT cost-effectiveness ratio was $2142 per quality-adjusted life-year. A mean number of 12.3 (95% CI, 12.0-12.5) and 2.0 (95% CI, 1.9-2.1) allergic reactions occurred in the POIT and avoidance groups over 20 years of simulation, with 2.3 (95% CI, 2.2-2.3) episodes of anaphylaxis treated with intramuscular epinephrine per subject in the POIT group and 1.1 (95% CI, 1.0-1.2) episodes per subject in the avoidance group. In sensitivity analyses, POIT was associated with lower rates of anaphylaxis than strict avoidance when the annual rate of accidental allergic reactions in the peanut avoidance group exceeded 25%, the annual rate of anaphylaxis in the POIT group dropped below 6%, or the probability of sustained unresponsiveness after 4 years of POIT was 68% or greater. CONCLUSIONS: POIT may be cost-effective in a long-term economic model. However, treated patients may experience a greater rate of peanut-associated allergic reactions and anaphylaxis. The analysis was sensitive to rates of accidental allergic reactions, therapy-associated adverse events, and likelihood of therapy-induced tolerance.

Molecular diagnosis and immunotherapy.

PURPOSE OF REVIEW: To describe recent insights into how molecular diagnosis can improve indication and selection of suitable allergens for specific immunotherapy and increase the safety of this therapy. RECENT FINDINGS: As specific allergen immunotherapy targets specific allergens, identification of the disease-eliciting allergen is a prerequisite for accurate prescription of treatment. In areas of complex sensitization to aeroallergens or in cases of hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may lead to a change in indication and selection of allergens for immunotherapy in a large proportion of patients when compared with diagnosis based on skin prick testing and/or specific IgE determination with commercial extracts. These changes in immunotherapy prescription aided by molecular diagnosis have been demonstrated to be cost-effective in some scenarios. Certain patterns of sensitization to grass or olive pollen and bee allergens may identify patients with higher risk of adverse reaction during immunotherapy. SUMMARY: Molecular diagnosis, when used with other tools and patients' clinical records, can help clinicians better to select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions. The pattern of sensitization to allergens could potentially predict the efficacy of allergen immunotherapy provided that these immunotherapy products contain a sufficient amount of these allergens. Nevertheless, multiplex assay remains a third-level approach, not to be used as screening method in current practice.

Non-adherence to subcutaneous allergen immunotherapy: inadequate health insurance coverage is the leading cause.

BACKGROUND: To sustain the long-lasting beneficial effects of subcutaneous allergen immunotherapy, the recommended duration of treatment is 3 to 5 years. Nevertheless, many patients discontinue allergy injections prematurely and therefore might not appreciate the full therapeutic benefit. OBJECTIVE: To examine factors leading to premature discontinuation of subcutaneous allergen immunotherapy (cessation before completion of the recommended duration). METHODS: Patients who discontinued immunotherapy before the completion of the prescribed duration and received their final injection from January 2008 through September 2013 were contacted to identify the reason for stopping the allergy injections. Phase of treatment (escalation or maintenance) was used to measure the duration of treatment at the time of cessation and patients were grouped accordingly. RESULTS: The study population consisted of 555 patients with allergic rhinitis and/or asthma who terminated immunotherapy prematurely. Two hundred thirteen (38%) were men and 342 (62%) were women. The following reasons were cited by patients for non-adherence to immunotherapy: requirement of copayment for allergy injections and/or payment for allergen extract by their health insurer (40%); inconvenience of travel (15%); change of residence (8%); concurrent health problems (5%); patient-perceived ineffectiveness (4%); patient-perceived lack of need to continue immunotherapy (2%); adverse effects from injection (local reaction 1%; systemic allergic reaction 0.5%); and trial of alternative medicine (0.1%). The remaining 24.4% did not provide a reason for discontinuation. CONCLUSION: Of the various factors, inadequate reimbursement for allergen extract and allergy injections by health insurers is the most common reason cited for non-adherence to subcutaneous allergen immunotherapy.

Selection of patients for sublingual versus subcutaneous immunotherapy.

Allergen immunotherapy is the sole treatment for IgE-mediated allergic diseases directed at the underlying mechanism. The two widely accepted administration routes are sublingual (SLIT) and subcutaneous (SCIT). We reviewed how patients should best be selected for immunotherapy and how the optimal administration route can be defined. Before deciding SCIT or SLIT, appropriate selection of patients for allergen immunotherapy (AIT) is mandatory. To be eligible for AIT, subjects must have a clear medical history of allergic disease, with exacerbation of symptoms on exposure to one or more allergens and a corresponding positive skin or in vitro test. Then the route of administration should be based on: published evidence of clinical and immunologic efficacy (which varies per allergic disease and per allergen); mono- or multi-allergen immunotherapy, for SLIT multi-allergen immunotherapy was not effective; safety: adverse events with SLIT are more frequent, but less severe; and, costs and patient preferences, closely related to adherence issues. All these are discussed in the article.

Patient-reported outcomes and quality-of-life questionnaires in the assessment of rhinoconjunctivitis in childhood.

PURPOSE OF REVIEW: Rhinoconjunctivitis, and especially allergic rhinoconjunctivitis (ARC) are increasing in prevalence, progressively affecting the well being of more and more adults and children. Clinical trials using allergen immunotherapy (AIT), the sole causal treatment of allergies, are being conducted, but discussions on optimal patient-related outcomes (PROs) are still ongoing. RECENT FINDINGS: Almost all publications discussing PROs relate to adults. The authors comment on the importance of broader PROs when assessing the results of AIT trials, as focusing on only nasal symptom improvement and medication reduction does not capture the full benefit of AIT. Such intervention also improves comorbid allergic diseases and general well being. In studies on rhinoconjunctivitis in children, using medical treatment or immunotherapy published between November 2012 - February 2014 nasal symptom (and medication) scores were primary outcomes in 18 of 20 trials. Only two trials applied quality-of-life questionnaires. SUMMARY: Clinical trials conducted in children with ARC should be interpreted with caution, as most currently used PROs give a restricted view, by not considering disease manifestations beyond nasal/ocular symptoms. To correctly estimate the full benefit of AIT in pediatric patients with ARC, broader PROs should be investigated, including disease control and quality of health.

Sublingual or subcutaneous immunotherapy for seasonal allergic rhinitis: an indirect analysis of efficacy, safety and cost.

RATIONALE, AIMS AND OBJECTIVES: The standard of preventive care for poorly controlled seasonal allergic rhinitis (AR) is subcutaneous immunotherapy (SCIT) with allergen extracts, administered in a physician's office. As an alternative to SCIT, sublingual immunotherapy (SLIT) is now an option for patients with seasonal AR. Oralair, a SLIT tablet containing freeze-dried allergen extracts of five grasses [cocksfoot (Dactylis glomerata), meadow grass (Poa pratensis), rye grass (Lolium perenne), sweet vernal grass (Anthoxanthum odoratum) and timothy grass (Phleum pratense)], and Grazax, a SLIT tablet containing a standardized extract of grass pollen allergen from timothy grass (P pratenase), are two such agents currently available in many countries. However, head-to-head comparative data are not available. In this study, an indirect comparison on efficacy, safety and cost was undertaken between Oralair, Grazax and SCIT. METHODS: A systematic review was conducted for double-blind placebo-controlled randomized trials evaluating Oralair, Grazax or SCIT in patients with grass-induced seasonal AR. Using placebo as the common control, an indirect statistical comparison between treatments was performed using meta regression analysis with active drug as the primary independent variable. An economic analysis, which included both direct and indirect costs for the Canadian setting, was also undertaken. RESULTS: Overall, 20 placebo-controlled trials met the study inclusion criteria. The indirect analysis suggested improved efficacy with Oralair over SCIT [standardized mean difference (SMD) in AR symptom control = -0.21; P = 0.007] and Grazax (SMD = -0.18; P = 0.018). In addition, there were no significant differences in the risk of discontinuation due to adverse events between therapies. Oralair was associated with cost savings against year-round SCIT ($2471), seasonal SCIT ($948) and Grazax ($1168) during the first year of therapy. CONCLUSIONS: Oralair has at least non-inferior efficacy and comparable safety against SCIT and Grazax at a lower annual cost.